11-92352397-G-C

Position:

• chr11-92352397-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001367949.2(FAT3):​c.285G>C​(p.Glu95Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,804 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FAT3 NM_001367949.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.363

Genes affected

FAT3 (HGNC:23112): (FAT atypical cadherin 3) Predicted to enable calcium ion binding activity. Predicted to be involved in cell-cell adhesion. Predicted to act upstream of or within several processes, including negative regulation of dendrite development; neuron migration; and retina layer formation. Predicted to be located in dendrite and plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAT3	NM_001367949.2	c.285G>C	p.Glu95Asp	missense_variant	2/28	ENST00000525166.6	NP_001354878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAT3	ENST00000525166.6	c.285G>C	p.Glu95Asp	missense_variant	2/28	5	NM_001367949.2	ENSP00000432586
FAT3	ENST00000409404.6	c.285G>C	p.Glu95Asp	missense_variant	1/25	5		ENSP00000387040	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458804 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725716

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2021

The c.285G>C (p.E95D) alteration is located in exon 1 (coding exon 1) of the FAT3 gene. This alteration results from a G to C substitution at nucleotide position 285, causing the glutamic acid (E) at amino acid position 95 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	0.93	D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D
Vest4		0.77
MutPred		0.36		Loss of loop (P = 0.1242);
MVP		0.63
ClinPred		0.92	D
GERP RS		1.5
Varity_R		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-92085563;